Triethylenethiophosphoramide is a specific inhibitor of cytochrome P4502B6: Implications for cyclophosphamide metabolism
Triethylenethiophosphoramide is a specific inhibitor of cytochrome P4502B6: Implications for cyclophosphamide metabolism
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DOI：
10.1124/dmd.30.5.525
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发表时间：
2002-05-01
影响因子：
3.9
通讯作者：
Desta, Z
中科院分区：
文献类型：
--
作者：
Rae, JM;Soukhova, NV;Desta, Z
Cytochrome P450 2B6 is a genetically polymorphic enzyme that is important in the metabolism of a number of clinically used drugs. This enzyme is not as well studied as other cytochrome P450 (P450) isoforms because of the lack of specific antibodies, probe drugs, and inhibitors. Although recent progress has been made toward specific antibodies and probe drugs, a specific enzyme inhibitor is still lacking. Studies suggest that CYP2B6 plays an important role in the 4-hydroxylation of cyclophosphamide and that this reaction can be inhibited by triethylenethiophosphoramide (thioTEPA). We therefore wished to test the hypothesis that thioTEPA is an inhibitor of CYP2B6. Using human liver microsomes (HLMs) and recombinant P450 enzymes, we demonstrated that thioTEPA is a potent and specific inhibitor of CYP2B6. Enzyme activity was reduced 78.1 +/- 0.2% by 50 muM thioTEPA when CYP2B6 activity was measured by following the metabolism of 200 muM S-mephenytoin to nirvanol. thioTEPA did not significantly inhibit (
